Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment.
DNA methylation analysis
DNA repair mechanisms
N of 1 experiment
RNA sequencing
combination cancer therapy
exceptional response to therapy
integrating molecular and clinical data
multi-platform genomic analyses
precision cancer medicine
rare mutations
synthetic lethality
whole-exome sequencing
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
11 01 2021
11 01 2021
Historique:
received:
23
06
2020
revised:
23
08
2020
accepted:
13
10
2020
pubmed:
21
11
2020
medline:
24
6
2021
entrez:
20
11
2020
Statut:
ppublish
Résumé
A small fraction of cancer patients with advanced disease survive significantly longer than patients with clinically comparable tumors. Molecular mechanisms for exceptional responses to therapy have been identified by genomic analysis of tumor biopsies from individual patients. Here, we analyzed tumor biopsies from an unbiased cohort of 111 exceptional responder patients using multiple platforms to profile genetic and epigenetic aberrations as well as the tumor microenvironment. Integrative analysis uncovered plausible mechanisms for the therapeutic response in nearly a quarter of the patients. The mechanisms were assigned to four broad categories-DNA damage response, intracellular signaling, immune engagement, and genetic alterations characteristic of favorable prognosis-with many tumors falling into multiple categories. These analyses revealed synthetic lethal relationships that may be exploited therapeutically and rare genetic lesions that favor therapeutic success, while also providing a wealth of testable hypotheses regarding oncogenic mechanisms that may influence the response to cancer therapy.
Identifiants
pubmed: 33217343
pii: S1535-6108(20)30546-8
doi: 10.1016/j.ccell.2020.10.015
pmc: PMC8478080
mid: NIHMS1649054
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
38-53.e7Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM122741
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA143843
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 CA999999
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201700005I
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201700005C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210969
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210988
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Interests P.W.L. is a member of the Scientific Advisory Board for AnchorDX. H.S.’s husband is part of the Scientific Advisory Board for AnchorDX. N.D. is employed by Foundation Medicine and holds Roche stock. A.J. was an employee of and had ownership interest in Foundation Medicine. V.M. was an employee of and had ownership interest in Foundation Medicine (through 12/31/2019) and is an equity shareholder of Mirati Therapeutics, Inc; on the Board of Directors, compensated by and an equity shareholder of Revolution Medicines, Inc.; a part-time employee and equity shareholder of EqRx (since March 2020); and holds patents with the USPO: 8501413, 8067175 (held by Sloan-Kettering Institute for Cancer Research and licensed to Molecular MD). All other authors declare no competing interests.
Références
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nucleic Acids Res. 2018 Nov 16;46(20):e123
pubmed: 30085201
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
Cell Rep. 2019 Nov 5;29(6):1675-1689.e9
pubmed: 31693904
Neuro Oncol. 2015 Oct;17(10):1356-64
pubmed: 25740784
Immunity. 2013 Oct 17;39(4):782-95
pubmed: 24138885
Investig Clin Urol. 2018 Sep;59(5):285-296
pubmed: 30182073
Genome Res. 2012 Mar;22(3):568-76
pubmed: 22300766
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Mutat Res Genet Toxicol Environ Mutagen. 2015 Nov;793:19-29
pubmed: 26520369
Nucleic Acids Res. 2019 Jan 8;47(D1):D994-D1004
pubmed: 30407583
Science. 1997 Nov 7;278(5340):1064-8
pubmed: 9353181
Biopreserv Biobank. 2018 Aug;16(4):247-250
pubmed: 29920119
N Engl J Med. 2011 Feb 10;364(6):501-13
pubmed: 21306237
Cancer Cell. 2010 Jan 19;17(1):13-27
pubmed: 20060365
Science. 2002 Jul 5;297(5578):63-4
pubmed: 12098689
J Natl Cancer Inst. 2021 Jan 4;113(1):27-37
pubmed: 32339229
Cell Rep. 2019 Apr 16;27(3):971-986.e9
pubmed: 30995489
Nature. 2000 Feb 3;403(6769):503-11
pubmed: 10676951
BMC Bioinformatics. 2010 Feb 18;11:94
pubmed: 20167110
Cancer Discov. 2017 Aug;7(8):818-831
pubmed: 28572459
Cell. 2019 Nov 14;179(5):1191-1206.e21
pubmed: 31730857
Hum Pathol. 2003 Jan;34(1):18-27
pubmed: 12605362
Brief Bioinform. 2021 May 20;22(3):
pubmed: 32789507
Nature. 2020 Jan;577(7791):549-555
pubmed: 31942075
Nature. 2011 Jun 29;474(7353):609-15
pubmed: 21720365
Nature. 2020 Jan;577(7791):556-560
pubmed: 31942077
Epigenomics. 2016 Mar;8(3):389-99
pubmed: 26673039
Cell. 2010 Jun 25;141(7):1117-34
pubmed: 20602996
J Immunother Cancer. 2017 Feb 21;5:18
pubmed: 28239471
Mutat Res Rev Mutat Res. 2016 Jul-Sep;769:19-35
pubmed: 27543314
N Engl J Med. 2004 Nov 18;351(21):2159-69
pubmed: 15548776
Nature. 2014 Feb 27;506(7489):445-50
pubmed: 24553142
Cancer Discov. 2014 Sep;4(9):1014-21
pubmed: 24934408
Hum Mol Genet. 2011 Jul 1;20(13):2603-10
pubmed: 21505078
J Pathol. 2018 Jul;245(3):283-296
pubmed: 29604063
Exp Hematol. 2016 Jul;44(7):603-13
pubmed: 27181063
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Clin Cancer Res. 2019 Mar 1;25(5):1535-1545
pubmed: 30523021
N Engl J Med. 2015 Aug 20;373(8):726-36
pubmed: 26287849
Clin Cancer Res. 2007 Mar 1;13(5):1532-9
pubmed: 17332299
Mol Cancer Ther. 2015 Apr;14(4):847-56
pubmed: 25695955
Nucleic Acids Res. 2013 Apr;41(7):e90
pubmed: 23476028
Nucleic Acids Res. 2019 Jan 8;47(D1):D23-D28
pubmed: 30395293
Cell Rep. 2018 Apr 03;23(1):239-254.e6
pubmed: 29617664
Nat Genet. 2015 Dec;47(12):1426-34
pubmed: 26551670
Genome Biol. 2011 Jul 25;12(7):R68
pubmed: 21787409
J Clin Oncol. 2015 Jun 10;33(17):1902-9
pubmed: 25847936
Science. 2012 Oct 12;338(6104):221
pubmed: 22923433
Genome Res. 2012 Sep;22(9):1760-74
pubmed: 22955987
Nature. 2020 Jan;577(7791):561-565
pubmed: 31942071
Gynecol Oncol. 2017 Sep;146(3):588-595
pubmed: 28709704
Nucleic Acids Res. 2017 Jan 4;45(D1):D777-D783
pubmed: 27899578
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nature. 2017 Mar 2;543(7643):122-125
pubmed: 28178237
Bioinformatics. 2009 Nov 1;25(21):2865-71
pubmed: 19561018
Hum Mutat. 2015 Apr;36(4):E2423-9
pubmed: 25703262
Cell. 2019 Aug 8;178(4):933-948.e14
pubmed: 31398344
Angew Chem Int Ed Engl. 2016 Feb 18;55(8):2911-5
pubmed: 26798972
Arch Pathol Lab Med. 1985 Aug;109(8):716-21
pubmed: 3893381
N Engl J Med. 2001 Mar 15;344(11):783-92
pubmed: 11248153
Cold Spring Harb Symp Quant Biol. 2017;82:329-338
pubmed: 29686033
N Engl J Med. 2001 Apr 5;344(14):1031-7
pubmed: 11287972
Nat Rev Mol Cell Biol. 2011 Feb;12(2):90-103
pubmed: 21252998
Nat Biotechnol. 2014 Sep;32(9):896-902
pubmed: 25150836
Nature. 2019 Nov;575(7784):699-703
pubmed: 31748743
N Engl J Med. 2010 Oct 28;363(18):1693-703
pubmed: 20979469
N Engl J Med. 2015 Jun 25;372(26):2481-98
pubmed: 26061751
Cell Mol Life Sci. 2010 Nov;67(21):3621-31
pubmed: 20809131
Mol Cell. 2014 Jan 9;53(1):7-18
pubmed: 24316220
Clin Cancer Res. 2012 Mar 15;18(6):1777-89
pubmed: 22422409
Nucleic Acids Res. 2017 Feb 28;45(4):e22
pubmed: 27924034
Immunity. 2018 Dec 18;49(6):1148-1161.e7
pubmed: 30552023
PLoS Comput Biol. 2011 May;7(5):e1001138
pubmed: 21625565